Antenatal Multiple Micronutrient Supplementation Research Articles

Multiple micronutrient supplementation cost-benefit tool for informing maternal nutrition policy and investment decisions.

Antenatal multiple micronutrient supplementation (MMS) is an intervention that can help reach three of the six global nutrition targets, either directly or indirectly: a reduction in low birth weight, stunting, and anaemia in women of reproductive age. To support global guideline development and national decision-making on investments into maternal nutrition, Nutrition International developed a modelling tool called the MMS cost-benefit tool to help users understand whether antenatal MMS is better value for money than iron and folic acid supplementation (IFAS) during pregnancy. The MMS cost-benefit tool can generate estimates on the potential health impact, budget impact, economic value, cost-effectiveness and benefit-cost ratio of investing in MMS compared to IFAS in LMICs. In the 33 countries with data included in the tool, the MMS cost-benefit tool shows that transitioning is expected to generate substantial health benefits in terms of morbidity and mortality averted and can be very cost-effective in multiple scenarios for these countries. The cost per DALY averted averages at US$ 23.61 and benefit-cost ratio ranges from US$ 41-US$ 1304: $1.0, which suggest MMS is good value for money compared with IFAS. With its user-friendly design, open access availability, and online data-driven analytics, the MMS cost-benefit tool can be a powerful resource for governments and nutrition partners seeking timely and evidence-based analyses to inform policy-decision and investments towards the scale-up of MMS for pregnant women globally.

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age(SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birthand SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine testand recall of LMP. The effects of MMS versus IFA on birthweight, preterm birthand SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratiosof 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Effects of antenatal micronutrient supplementation regimens on adolescent emotional and behavioral problems: A 14-year follow-up of a double-blind, cluster-randomized controlled trial

Antenatal multiple micronutrient supplementation has been shown to have beneficial effects on birth outcomes and may improve child development. However, whether there is an effect of antenatal micronutrient supplementation strategies on offspring socioemotional outcomes remains unknown. We aimed to examine the effect of antenatal folic acid (FA), iron-folic acid (IFA), and multiple micronutrient (MMN) supplementation on adolescent emotional and behavioral outcomes. We conducted a double-blind, cluster-randomized trial of antenatal micronutrient supplementation in rural western China between 2002 and 2006. Pregnant females were randomized by village to receive either daily (i) 400μg FA, (ii) IFA containing 60mg iron and 400μg FA or (iii) MMN supplementation containing 30mg iron, 400μg FA plus 13 additional vitamins and minerals. A 14-year follow-up of their offspring was conducted in 2016. Adolescents were administered the locally adapted Youth Self-Report-2001 (YSR-2001) which produced internalizing, externalizing, and total behavior problem scores. We applied generalized estimating equations to assess the effect of the randomized regimens on YSR-2001 scores and explored the potential effect modification by household wealth and initial timing and duration of supplementation. A total of 1920 adolescents were included in the analysis, 1130 (58.9%) were male, and the mean (SD) age was 11.8 (0.78) years. Adolescents in IFA group had lower total (mean difference (MD):-2.89; 95% CI -5.73,-0.04) and externalizing (MD:-0.97; 95% CI -1.79,-0.15) problem scores as compared to those in FA group. There was no effect of MMN on behavior problem scores as compared to IFA and FA alone. Although, in effect modification analyses, MMN appeared to have greater beneficial effects in wealthier households than IFA and FA alone. Iron supplementation during pregnancy reduced adolescent emotional and behavioral problem scores which provides additional support for expanding coverage of iron-containing prenatal supplements in resource-limited settings. isrctn. org Identifier: ISRCTN08850194.

Antenatal Multiple Micronutrient Supplementation in the State of Palestine: A Protocol for Implementation and Evaluation

ObjectivesThe 2013 Palestinian Micronutrient Survey1 reported high and comparable 1st trimester prevalences of micronutrient deficiencies in the Gaza Strip and West Bank: 23.6% and 21.3% for iron, 67.9% and 49.6% for zinc, 11.4% and 8.8% for vitamin A, 27.9% and 19.1% for B12, 78.6% and 66.7% for vitamin D and 17.5% and 13.2% for vitamin E, respectively. Rates were generally higher among gravida in their 2nd-3rd trimesters. Interim, clinic-based, anemia rates2 in the Gaza Strip and West Bank of 32% and 19% in the first trimester and 71% and 38% in the 2nd and 3rd trimesters, respectively, coupled with food insecurity, dietary inadequacy, civil conflict and stresses from the COVID-19 pandemic, suggest micronutrient deficiencies persist as a public health burden in the State of Palestine. To replace current iron-folic acid (IFA) with a multiple micronutrient supplement (MMS) providing a Recommended Dietary Allowance of 15 essential vitamins and minerals as standard of antenatal care (ANC) in UNWRA clinics and hot spots serving pregnant women in the Gaza (n = 22) in 2021–2 and West Bank (n = 44) in 2022–3. MethodsMMS is planned to start in Gaza in the Fall of 2021, where UNRWA antenatal services reach ∼38,000 pregnant women with IFA each year; ∼97% of whom attended ANC ≥ 4 times2. Implementation will follow a randomized, step-wedge procedure whereby MMS will start in the 1st 11 clinics, and six months later, the 2nd group of 11 clinics, providing a design for monitoring and comparing the new MMS to existing IFA programs during an initial 6–8 month period. ResultsOutcomes will include indicators of adoption, acceptability, coverage, adherence, fidelity, cost-efficiencies and, as a routine clinical outcome, late pregnancy anemia. ConclusionsMaternal micronutrient deficiencies are common in Palestine3, meriting replacing IFA with MMS. This research protocol will evaluate implementation in the Gaza Strip to provide guidance for launching and improving antenatal MMS delivery throughout the UNRWA health system. Funding SourcesUNWRA, Sight and Life, Kirk Humanitarian, Vitamin Angels Alliance, Ministry of Foreign Affairs of Japan, Palestine Ministry of Health.

Plasma Untargeted Metabolomic Profile Associated with Vitamin A Status in Pregnant Women in Rural Bangladesh

Abstract Objectives Vitamin A status during pregnancy is important for visual health, immune function and fetal growth and development. However, little is known about how vitamin A may affect systemic metabolic function of undernourished pregnant women. The objective of this study is to characterize metabolic signatures and pathways associated with vitamin A status in pregnant women. Methods This study was nested into JiVitA-3, a community-based antenatal multiple micronutrient vs. iron-folic acid supplementation trial in rural Bangladesh. In plasma samples of 150 women at ∼32 weeks of gestation, retinol had been measured by HPLC and relative abundances of metabolites were measured by UPLC Q-Exactive HF-X mass spectrometer. Univariate linear regression was used to determine metabolites associated with plasma retinol. Multiple testing was corrected using a false discovery rate threshold of 5%. Results Among 2985 peak features included in data analysis, 97 known metabolites were positively or negatively associated with plasma retinol concentrations. Among the top 11 positive correlates, seven metabolites are tryptophan or its metabolic catabolites including 5-methoxy tryptophan, tryptamine, 5-methoxytryptamine, N-formylkynureine, indole, 2-indolecarboxylic acid, and 3-methylene-indolenine (r = 0.32∼0.42, p-value < 8 × 10−5). Pathway analysis demonstrated that metabolic pathways of tryptophan, nicotinamide (vitamin B3), lysine, arginine and proline were significantly enriched (gamma p-value < 0.05). Conclusions An untargeted plasma metabolomics platform revealed associations of microbial catabolites of tryptophan and other amino acids with vitamin A status of undernourished pregnant women. These metabolites have been implicated in activation of intestinal immune cells and anti-inflammatory and anti-oxidative functions. The results suggest novel mechanisms by which vitamin A may influence immune system and systemic homeostasis, prompting a need for confirmatory studies. Funding Sources The JiVitA-3 trial and micronutrient status assessments were funded by the Bill and Melinda Gates Foundation (West, PI). Metabolomics analysis was funded from the NIH Common Fund Metabolomics Program (Sumner, PI).

What Works for Maternal and Child Undernutrition: A Review of the Evidence

Background: Policy and programming to improve maternal and child nutrition has become a mainstay of most countries because of the direct implications of nutrition on population health, economic development, and human capital. Since the 2013 Lancet Nutrition series, more evidence on the set of 10 recommended interventions has emerged, along with evidence for newer interventions. This paper primarily aims to determine what works in the current low and middle-income country (LMIC) context to improve maternal and child undernutrition. Methods: We undertook ten new systematic reviews that examined the impact of direct and indirect nutrition interventions on maternal, newborn, child, and adolescent health and nutrition with a focus on LMICs. We used the PICO methodology to construct our search strategies; appropriate syntax was applied to key words and MeSH terms/key words were combined with Boolean operators. Searches were run in all relevant databases, which varied depending on the research question, and grey literature searches were conducted in Google, Google Scholar, and within websites of key nutrition organizations. Review updates were also undertaken. Results from our reviews and review updates were triangulated with other, high-quality published evidence of intervention effects. Findings: The updated evidence underscores the effectiveness of the ten interventions recommended in the 2013 Lancet Nutrition Series including periconceptional folic acid supplementation or fortification, maternal balanced energy protein supplementation, maternal calcium supplementation, maternal multiple micronutrient supplementation, promotion of breast feeding, appropriate complementary feeding, vitamin A and preventive zinc supplementation in children 6-59 months of age, and management of severe- and moderate-acute malnutrition. The evidence for antenatal multiple micronutrient supplementation has strengthened, with greater effects on stillbirths and babies born preterm, small for gestational age and with low birthweight compared to iron-folic acid supplementation. Emerging interventions with evidence of effects on child growth outcomes include small-quantity lipid-nutrient supplements for children 6-23 months of age and kangaroo mother care for healthy term and late preterm neonates through facility and community-based approaches. Evidence supports the provision of supplementary food to pregnant women and children residing in food-insecure settings, and community-based approaches to manage children with acute malnutrition with locally produced supplementary and therapeutic food. Indirect nutrition strategies, such as malaria prevention, preconception care, and water, sanitation, and hygiene, may provide nutritional benefits in some settings. Interpretation: Evidence continues to support the direct nutrition interventions and the indirect health and nutrition interventions recommended in 2013. Additionally, small-quantity lipid-nutrient supplements and kangaroo mother care should be considered for scale up in LMICs to improve growth and micronutrient status. The coverage of priority interventions remains low, especially in contexts where they are needed most. Hence, greater focus and effort are required to improve the reach of these interventions, especially for the most vulnerable populations. There is also a need to develop evidence-based strategies to address undernutrition in school-age children and adolescents. Funding Statement: This study was funded by the Bill & Melinda Gates Foundation with additional support from the Centre for Global Child Health, the Hospital for Sick Children, Toronto and the Center of Excellence in Women and Child Health, the Aga Khan University, Karachi, Pakistan. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: Not required.

Antenatal multiple micronutrient supplementation: where are the long‐term benefits?

Antenatal multiple micronutrient supplementation: where are the long‐term benefits?

Antenatal Multiple Micronutrient Supplementation Compared to Iron–Folic Acid Affects Micronutrient Status but Does Not Eliminate Deficiencies in a Randomized Controlled Trial Among Pregnant Women of Rural Bangladesh

ABSTRACTBackgroundAntenatal multiple micronutrient (MM) supplementation improves birth outcomes relative to iron–folic acid (IFA) in developing countries, but limited data exist on its impact on pregnancy micronutrient status.ObjectiveWe assessed the efficacy of a daily MM (15 nutrients) compared with IFA supplement, each providing approximately 1 RDA of nutrients and given beginning at pregnancy ascertainment, on late pregnancy micronutrient status of women in rural Bangladesh. Secondarily, we explored other contributors to pregnancy micronutrient status.MethodsWithin a double-masked trial (JiVitA-3) among 44,500 pregnant women, micronutrient status indicators were assessed in n = 1526 women, allocated by cluster to receive daily MM (n = 749) or IFA (n = 777), at 10 wk (baseline: before supplementation) and 32 wk (during supplementation) gestation. Efficacy of MM supplementation on micronutrient status indicators at 32 wk was assessed, controlling for baseline status and other covariates (e.g., inflammation and season), in regression models.ResultsBaseline status was comparable by intervention. Prevalence of deficiency among all participants was as follows: anemia, 20.6%; iron by ferritin, 4.0%; iron by transferrin receptor, 4.7%; folate, 2.5%; vitamin B-12, 35.4%; vitamin A, 6.7%; vitamin E, 57.7%; vitamin D, 64.0%; zinc, 13.4%; and iodine, 2.6%. At 32 wk gestation, vitamin B-12, A, and D and zinc status indicators were 3.7–13.7% higher, and ferritin, γ-tocopherol, and thyroglobulin indicators were 8.7–16.6% lower, for the MM group compared with the IFA group, with a 15–38% lower prevalence of deficiencies of vitamins B-12, A, and D and zinc (all P < 0.05). However, indicators typically suggested worsening status during pregnancy, even with supplementation, and baseline status or other covariates were more strongly associated with late pregnancy indicators than was MM supplementation.ConclusionsRural Bangladeshi women commonly entered pregnancy deficient in micronutrients other than iron and folic acid. Supplementation with MM improved micronutrient status, although deficiencies persisted. Preconception supplementation or higher nutrient doses may be warranted to support nutritional demands of pregnancy in undernourished populations. This trial was registered at clinicaltrials.gov as NCT00860470.

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries.

Inadequate micronutrient intakes are relatively common in low‐ and middle‐income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost‐effectiveness of MMS compared with IFA. Recent meta‐analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual‐participant data meta‐analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost‐effective method to reduce the risk of adverse birth outcomes.

Association of Antenatal Micronutrient Supplementation With Adolescent Intellectual Development in Rural Western China

The association of micronutrient supplementation during pregnancy with the intellectual development of adolescent offspring is unknown. To assess the long-term association of antenatal micronutrient supplementation with adolescent intellectual development. This 14-year follow-up study of a randomized clinical trial of micronutrient supplementation in pregnancy was conducted in 2 counties in rural western China in 2118 adolescent offspring (aged 10 to 14 years) of mothers who were randomized to take a daily capsule of either folic acid, folic acid plus iron, or multiple micronutrients from August 1, 2002, through February 28, 2006. Follow-up was conducted from June 1, 2016, through December 31, 2016. Data analyses took place from April 1, 2017, to June 20, 2017. Adolescent full-scale intelligence quotient and aspects of verbal comprehension, working memory, perceptual reasoning, and processing speed indexes were assessed by the Wechsler Intelligence Scale for Children. Of 2118 adolescent offspring, 1252 (59.1%) were boys and 866 (40.9%) were girls, with a mean (SD) age of 11.7 (0.87) years, representing 47.2% of the 4488 single live births that were eligible to participate. Compared with folic acid supplementation, multiple micronutrient supplementation was associated with a 1.13-point higher full-scale intelligence quotient (95% CI, 0.15-2.10) and a 2.03-point higher verbal comprehension index (95% CI, 0.61-3.45); similar results were found in comparison with folic acid plus iron. When mothers initiated supplementation early (<12 weeks of gestation) and had an adequate dose (≥180 capsules), multiple micronutrient capsules were associated with a 2.16-point higher full-scale intelligence quotient (95% CI, 0.41-3.90) and 4.29-point higher verbal comprehension index (95% CI, 1.33-7.24) compared with folic acid capsules. The mean test scores were lower in the substratum of supplementation initiated late (≥12 weeks of gestation) and with an inadequate dose (<180 capsules). The multiple micronutrient group had higher scores than the other 2 treatment groups, and significant differences were observed for full-scale intelligence quotient (adjusted mean difference, 2.46; 95% CI, 0.98-3.94) when compared with the folic acid plus iron group. Compared with folic acid plus iron or folic acid capsules supplementation, antenatal multiple micronutrient supplementation appeared to be associated with increased adolescent intellectual development; initiating supplementation in the first trimester and then continuing for at least 180 days were associated with the greatest rewards. isrctn.org Identifier: ISRCTN08850194.

Antenatal multiple micronutrient supplementation: benefits beyond iron-folic acid alone.

Antenatal multiple micronutrient supplementation: benefits beyond iron-folic acid alone.

Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis.

BackgroundMultiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries (LMICs) to improve child survival, growth and health. We aimed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or second trimester.MethodsWe searched systematically for follow-up reports from all trials in a 2015 Cochrane review of multiple micronutrient supplementation in pregnancy. The intervention comprised three or more micronutrients and the comparison group received iron (60 mg) and folic acid (400 μg), where possible. Median gestation of commencement varied from 9 to 23 weeks. Primary outcomes were offspring mortality, height, weight and head circumference, presented as unadjusted differences in means or proportions (intervention minus control). Secondary outcomes included other anthropometry, body composition, blood pressure, and cognitive and lung function.ResultsWe found 20 follow-up reports from nine trials (including 88,057 women recruited), six of which used the UNIMMAP supplement designed to provide recommended daily allowances. The age of follow-up ranged from 0 to 9 years. Data for mortality estimates were available from all trials. Meta-analysis showed no difference in mortality (risk difference –0.05 per 1000 livebirths; 95 % CI, –5.25 to 5.15). Six trials investigated anthropometry and found no difference at follow-up in weight-for-age z score (0.02; 95 % CI, –0.03 to 0.07), height-for-age z score (0.01; 95 % CI, –0.04 to 0.06), or head circumference (0.11 cm; 95 % CI, –0.03 to 0.26). No differences were seen in body composition, blood pressure, or respiratory outcomes. No consistent differences were seen in cognitive function scores.ConclusionsThere is currently no evidence that, compared with iron and folic acid supplementation, routine maternal antenatal multiple micronutrient supplementation improves childhood survival, growth, body composition, blood pressure, respiratory or cognitive outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0633-3) contains supplementary material, which is available to authorized users.

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal.

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at 2 years of age in offspring, compared to those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function by measuring spirometry at 7-9 years of age in C: hildren born during the trial. 841 children (80% of the cohort) were seen at mean±sd 8.5±0.4 years. Technically successful spirometry results were obtained in 793 (94.3%) children, 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95% CI) difference in z-scores (supplementation minus control) was -0.08 (-0.19-0.04), -0.05 (-0.17-0.06) and -0.04 (-0.15-0.07) for forced expiratory volume in 1 s (FEV1), forced vital capacity and FEV1/FVC, respectively. Compared with healthy white children, FEV1 and FVC in the "healthy" Nepalese children were ∼1 (∼13%) z-score lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age.

The Effect of Antenatal Multiple Micronutrient Supplementation on Placental Angiogenesis and Fetal Growth Factors in Rural Bangladesh

The Effect of Antenatal Multiple Micronutrient Supplementation on Placental Angiogenesis and Fetal Growth Factors in Rural Bangladesh

The Health Effects of Antenatal Multiple Micronutrient Supplementation in Nepalese Children

The Health Effects of Antenatal Multiple Micronutrient Supplementation in Nepalese Children

Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial.

Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. clinicaltrials.gov Identifier: NCT00860470.

Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial.

SummaryBackgroundIn 2002–04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these differences would be sustained.MethodsFor this follow-up study, we identified children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-for-age according to WHO Child Growth Standards for children aged 5–19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934.FindingsBetween Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted differences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI −0·09 to 0·19), 0·02 in height-for-age (−0·10 to 0·15), and 0·04 in BMI-for-age (−0·09 to 0·18). We recorded no difference in blood pressure. Adjusted differences were similar for all outcomes.InterpretationWe recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our findings did not extend to physiological differences or potential longer-term effects.FundingThe Wellcome Trust.

P04 The phenotypic effects of antenatal multiple micronutrient supplementation in Nepalese children

BackgroundA growing body of evidence suggests that changes in early-life environment can have lasting effects. To investigate this, we followed up children from a double-blind randomised controlled trial of antenatal...

Antenatal multiple micronutrient supplementation and growth in the first two years of life and cognitive function at 24 months in rural Bangladesh (256.5)

In a cluster‐randomized, controlled trial in rural Bangladesh, antenatal multiple micronutrient (MM) vs. iron‐folic acid (IFA) supplementation enhanced birth weight and length. We assessed the effects of the intervention on growth at 1, 3, 6, 12 and 24 mo of age and cognitive function using Bayley‐III at 24 mo. Children were born with low mean (SD) length for age Z‐score (LAZ) of ‐1.58 (1.20) in the MM and ‐1.69 (1.26) in the IFA group (p&lt;0.001). Linear growth improved over the first 6 months in both groups. MM increased LAZ by mean (SE) 0.06 (0.01), at both 1 and 3 mo of age compared to IFA after adjusting for birth LAZ and design effect (both p&lt;0.001). Stunting prevalence was lower at 1 mo (32.2 vs. 36.0%, RR=0.95, 95% CI:0.92, 0.98) and at 3 mo (24.5 vs. 29.0%, RR=0.91, 95%CI:0.88, 0.94) in the MM vs. IFA group, after adjusting for stunting at birth. The difference between groups was attenuated and not significant by 6 mo and absent by 12 and 24 mo of age, at which time stunting prevalance was 50%. In a substudy (n=750), there was no treatment effect on composite scores of cognition, language, and motor performance or behavior at 24 mo. MM supplementation improved postnatal linear growth beyond birth, but after supplement use had ended at 3 mo postpartum, and around the age of introduction of complementary foods at 6 months, the benefit on growth was no longer apparent, suggesting that infections and inadequate breastfeeding and complementary feeding practices have a strong influence on growth beyond 6 mo in this rural South Asian context.Grant Funding Source: Supported by the Bill &amp; Melinda Gates Foundation Grant 614

Effects of Antenatal Micronutrient Supplementation on Plasma Protein Profiles in Nepalese Children

Antenatal multiple micronutrient (MN) supplementation in malnourished settings may favor a healthy phenotype in offspring, but mechanisms remain largely unexplored. Plasma proteomics may offer a way to reveal long‐term metabolic effects of early MN exposure. We are applying quantitative mass spectrometry to explore differences in plasma protein abundance in 500 Nepalese children 6–8 yr of age born to mothers who were randomized (100 each) to receive daily supplements of folic acid (FA), iron+FA (IFA), IFA+zinc (IFAZ), multiple MNs, or placebo from 1st trimester to 6 wk postpartum. All tablets also contained vitamin A. Among ~980 plasma proteins measured in ≥ 10% of children, preliminary analysis reveals 9, 10, 8 and 14 proteins were differentially abundant in the FA, IFA, IFAZ and multiple MN vs. control group (all p&lt; 0.01). So far, insulin‐like growth factor‐binding protein 5, ATP‐binding cassette sub‐family A, and eukaryotic translation initiation factor 3 are differentially abundant from controls in 2 nutrient groups. Insulin‐like growth factor 1 was highly abundant in FA, IFAZ, and multiple MNs compared to placebo. Early life micronutrient exposure may influence early childhood plasma protein profiles by presumably interacting with genes regulating growth and development. Supported by the Bill and Melinda Gates Foundation (Grants GH5241 and GH614).Grant Funding Source: Bill and Melinda Gates Foundation